phosphocreatine and Multiple-Sclerosis--Chronic-Progressive

Abnormalities in normal-appearing brain tissues may contribute to disability in primary progressive multiple sclerosis (PPMS), where few lesions are seen on conventional imaging.. To evaluate the mechanisms underlying disease progression in the early phase of PPMS by measuring metabolite concentrations in normal-appearing white matter (NAWM) and cortical gray matter (CGM) and to assess their relationship with clinical outcomes.. Case-control study.. Tertiary referral hospital. Patients Forty-three consecutive patients within 5 years of onset of PPMS and 44 healthy control subjects.. Concentrations of choline-containing compounds, phosphocreatine, myo-inositol, total N-acetyl-aspartate (tNAA), and glutamate-glutamine were estimated using proton magnetic resonance spectroscopic imaging. Brain parenchymal, white matter and gray matter fractions and proton density and gadolinium-enhancing lesion loads were calculated. The Expanded Disability Status Scale and Multiple Sclerosis Functional Composite scores were recorded.. In CGM, concentrations of the tNAA (P<.001) and glutamate-glutamine (P = .005) were lower in patients with PPMS than in controls. In NAWM, myo-inositol levels were higher (P = .002) and tNAA levels were lower (P = .005) in patients with PPMS than in controls. The Expanded Disability Status Scale score correlated with the tNAA concentration in CGM (r = -0.44; P = .03) and with myo-inositol (r = 0.41; P = .01) and glutamate-glutamine concentrations (r = 0.41; P = .01) in NAWM. Proton density lesion load correlated negatively with CGM tNAA concentration and positively with NAWM myo-inositol concentration.. Metabolite changes, which differ in CGM and NAWM, occur in early PPMS and are linked with disability.

Topics: Adult; Age of Onset; Aged; Aspartic Acid; Biomarkers; Case-Control Studies; Cerebral Cortex; Choline; Disability Evaluation; Disease Progression; Female; Glutamic Acid; Humans; Inositol; Magnetic Resonance Spectroscopy; Male; Middle Aged; Multiple Sclerosis, Chronic Progressive; Nerve Fibers, Myelinated; Neurons; Neuropil; Phosphocreatine; Predictive Value of Tests; Reference Values; Statistics as Topic

Proton magnetic-resonance spectroscopy (PMRS) was used to measure the levels of inositol/myoinositol (Ins), choline, creatine/phosphocreatine (Cr), glutamine/glutamate (Glx/Glx1), N-acetylaspartate (NAA), gamma-aminobutyric acid (GABA) and lipids were measured in the foci of demyelinization in the brains of 59 patients with multiple sclerosis (MS). Magnetic-resonance imaging was performed during a single investigation. A control group comprised 20 healthy individuals. PMRS revealed significant alterations in the levels of metabolite in all the patients as compared with the controls: decreases in NAA by 23-52%, in Cr by 12-21%, in choline by 15-26%; increases in Ins by 51-63%; as well as the appearance of lipids (up to 100%). In MS, there were reduction in NAA/Cr, NAA/choline, and NAA/choline/Cr ratios by 12-53; 10-19; and 57-82%, respectively. As compared with the remitting MS, secondary-progressive MS showed decreases in the content of NAA by 23-25%, NAA/(choline + Cr) by 48-54% and increases in the levels of Ins and lipids by 50-76%. In remitting MS, there was a strong correlation between the NAA/Cr ratio and the volume brain lesion. It is concluded that PMRS evaluated the extent, pattern and activity of demyelinization (by the levels of Ins, NAA, Cr, lipids) and the intensity of cerebral atrophy (by NAA levels, NAA/Cr ratio). The findings testify that there are neurochemical differences between remitting and secondary-progressive MS.

Topics: Adolescent; Adult; Aspartic Acid; Brain; Choline; Creatine; Demyelinating Diseases; Female; gamma-Aminobutyric Acid; Glutamic Acid; Humans; Inositol; Magnetic Resonance Spectroscopy; Male; Multiple Sclerosis, Chronic Progressive; Multiple Sclerosis, Relapsing-Remitting; Phosphocreatine; Severity of Illness Index